mycophenolic-acid and Respiratory-Insufficiency

Systemic sclerosis (SSc) is an intractable disease that causes fibrosis in all organs. Approximately 40% of patients with SSc have some degree of interstitial lung disease (ILD). One third of patients with SSc and ILD, approximately 15% of all patients, have pulmonary lesions, which slowly progress to respiratory failure resistant to corticosteroid and other treatments. A randomized controlled trial conducted in the United States indicated that one year of treatment with oral cyclophosphamide in patients with SSc-ILD had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and health-related quality of life. However, all the effects, except for a sustained impact on dyspnea, disappeared approximately one year after stopping oral administration of cyclophosphamide. A randomized controlled trial using cyclophosphamide and mycophenolate mofetil (MMF) was then held in the United States for 142 patients with SSc-ILD. Treatment of SSc-ILD with MMF for two years or cyclophosphamide for one year both resulted in significant improvements in lung function over the 2-year course of the study. Leukopenia and thrombocytopenia occurred less often in patients administered MMF than in those administered cyclophosphamide. MMF is currently not approved for the treatment of SSc-ILD in Japan. Both MMF and cyclophosphamide were effective against ILD associated with SSc and, in particular, MMF was useful in terms of tolerability. When MMF is approved, it should be positioned as one of the first treatment options for SSc-ILD, which will further enhance the treatment of this disease in Japan.

Topics: Cyclophosphamide; Disease Progression; Humans; Leukopenia; Lung Diseases, Interstitial; Mycophenolic Acid; Randomized Controlled Trials as Topic; Respiratory Insufficiency; Scleroderma, Systemic; Thrombocytopenia

We aimed to identify clinical settings of renal transplant patients with COVID-19.. In this retrospective study, we included kidney transplant inpatients with laboratory confirmed COVID-19 who had been discharged or had died by October 1st, 2020. Characteristics of the patients, including basal and last outpatient biochemical parameters were recorded. Discontinuation or dosage reduction of immunosuppressives and other treatment information was documented.. Twenty patients were included in this study, of whom 18 were discharged and 2 died in hospital. The mean duration of hospitalization and follow-up were 9.7 ± 6.4 days and 4.5 ± 2.0 months, respectively. Fourteen patients (70%) were male and mean age was 48.0 ± 10.3 years. At admission, all had immunosuppression withdrawn and were started on methylprednisolone 16 mg/ day (50%) or dexamethasone (50%). Tacrolimus/m-TOR inhibitors were reduced by 50% and all antimetabolites were discontinued. Hemodialysis was needed for 10% of patients. Acute kidney injury was detected in 25% of the patients. With respect to hospitalization time and complications, there was no significant difference between patients who used dexamethasone and those who did not (P > 0.05). The discontinued immunosuppressives were resumed within 2 to 4 weeks after discharge according to the severity of disease. No rehospitalization or acute rejection was detected during the follow-up of the patients.. Renal transplant patients are considered a high risk group for COVID-19. It can be said that discontinuation or reducing dosages of immunosuppressives may be effective and safe in kidney transplant patients.

Topics: Acute Kidney Injury; Adult; COVID-19; Deprescriptions; Dexamethasone; Disease Progression; Everolimus; Female; Glucocorticoids; Graft Rejection; Hospital Mortality; Hospitalization; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Length of Stay; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Renal Dialysis; Respiration, Artificial; Respiratory Insufficiency; Retrospective Studies; SARS-CoV-2; Sepsis; Tacrolimus

The number of contrast media-related procedures is ever increasing due to the widespread availability of theoretically safe, low osmolar iodinated contrast material. Although intravenously administered contrast is known to precipitate myasthenic crisis, oral contrast aspiration as a causative factor is not yet documented as such. A 48-year-old Sinhalese man diagnosed as having myasthenia gravis, was evaluated for progressive dysphagia with an upper gastrointestinal contrast study. Iodinated contrast material (iohexol) was used as the contrast medium and there was direct evidence of contrast aspiration during the study. Several minutes after the procedure, severe respiratory distress with evidence of myasthenic crisis requiring intubation and intensive care admission was noted. Treatment with intravenous immunoglobulin, high-dose steroids, and broad-spectrum intravenously administered antibiotics led to an uneventful recovery, although the latter part of the clinical course was complicated with total left lung collapse. Myasthenic crisis can be precipitated by various factors and a successful recovery requires mechanical respiratory support with immunomodulatory and steroid therapy. This is the first reported case that describes the development of myasthenic crisis following iohexol-associated aspiration pneumonitis.

Topics: Cholinesterase Inhibitors; Contrast Media; Deglutition Disorders; Disease Progression; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Iohexol; Male; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Pneumonia, Aspiration; Pneumothorax; Prednisolone; Pyridostigmine Bromide; Respiration, Artificial; Respiratory Aspiration; Respiratory Insufficiency

Topics: Diaphragm; Dyspnea; Humans; Immunosuppressive Agents; Male; Myasthenia Gravis; Mycophenolic Acid; Oximetry; Plasma Exchange; Point-of-Care Testing; Prednisone; Respiration, Artificial; Respiratory Function Tests; Respiratory Insufficiency; Treatment Outcome; Ultrasonography; Young Adult

To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA).. The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons.. In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n = 48) or GPA (n = 183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil.. Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding.

Topics: Adolescent; Adrenal Cortex Hormones; Age Distribution; Antibodies, Antineutrophil Cytoplasmic; Asia; Azathioprine; Canada; Child; Child, Preschool; Cohort Studies; Cyclophosphamide; Drug Therapy, Combination; Europe; Female; Granulomatosis with Polyangiitis; Hemorrhage; Humans; Immunosuppressive Agents; Infant; Kidney Failure, Chronic; Lung Diseases; Male; Methotrexate; Microscopic Polyangiitis; Mycophenolic Acid; Nephrotic Syndrome; Oxygen Inhalation Therapy; Plasmapheresis; Proteinuria; Renal Dialysis; Respiratory Insufficiency; Rituximab; United States

Organising pneumonia (OP) is usually promptly responsive to corticosteroid treatment. We describe a series of 3 cases of severe, progressive, biopsy-proven fibrosing OP causing respiratory failure. All cases presented with peribronchial and subpleural consolidations, had a fibro-inflammatory infiltrative component in the alveolar septa, and only had a partial and unsatisfactory response to corticosteroids. However, they responded to mycophenolic acid (MPA) treatment with resolution of respiratory failure as well as clinical and functional improvement. MPA as an additional treatment option for aggressive forms of fibrosing OP and interstitial lung disease needs to be further explored.

Topics: Adult; Aged; Cryptogenic Organizing Pneumonia; Enzyme Inhibitors; Female; Fibrosis; Humans; Lung; Male; Middle Aged; Mycophenolic Acid; Radiography, Thoracic; Respiratory Insufficiency; Tomography, X-Ray Computed; Treatment Outcome

Advanced kidney disease is usually considered an absolute contraindication for lung transplantation due to the difficult management of these patients in the post-operative period. Combined lung-kidney transplantation, however, could offer an opportunity for selected patients with renal and pulmonary dysfunction. This study summarizes the long-term success of a double transplantation in a 38-year-old male patient with cystic fibrosis who presented respiratory and kidney failure. After a complicated post-operative period, the patient currently lives completely independently 46 months after the operation and he enjoys excellent pulmonary and renal function.

Topics: Acute Disease; Adult; Antibodies, Monoclonal; Basiliximab; Coinfection; Cystic Fibrosis; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Lung Transplantation; Male; Mycophenolic Acid; Pneumonia; Prednisone; Recombinant Fusion Proteins; Recovery of Function; Renal Dialysis; Respiratory Insufficiency; Tacrolimus

Topics: Acute Disease; Adult; Animals; Fatal Outcome; Female; Humans; Ivermectin; Kidney Transplantation; Larva; Mycophenolic Acid; Prednisone; Respiratory Insufficiency; Strongyloides stercoralis; Strongyloidiasis; Tacrolimus

The tuberculostatic compound rifampin (INN, rifampicin) induces the expression of a number of drug metabolism-related genes involved in multidrug resistance (P-glycoprotein and multidrug resistance proteins 1 and 2), cytochromes (cytochrome P450 [CYP] 3A4), uridine diphosphate-glucuronosyltransferases, monoamine oxidases, and glutathione S -transferases. Drugs that depend on these enzymes for their metabolism are prone to drug interactions when coadministered with rifampin. A novel, clinically relevant drug interaction is described between rifampin and mycophenolate mofetil (MMF), a cornerstone immunosuppressive molecule used in solid organ transplantation. Long-term rifampin therapy caused a more than twofold reduction in dose-corrected mycophenolic acid (MPA) exposure (dose-interval area under the concentration curve from 0 to 12 hours [AUC 0-12]) when administered simultaneously in a heart-lung transplant recipient, whereas subsequent withdrawal of rifampin resulted in reversal of these changes after 2 weeks of washout (dose-corrected AUC 0-12 after rifampin withdrawal, 19.7 mg.h.L-1.g -1 versus 6.13 mg.h.L-1.g-1 before rifampin withdrawal [221% change]; dose-uncorrected AUC 0-12 after rifampin withdrawal, 29.6 mg.h/L [daily MMF dose, 3 g] versus 18.4 mg.h/L [daily MMF dose, 6 g] during rifampin administration [60.8% change]). Failure to recognize this drug interaction could potentially lead to MPA underexposure and loss of clinical efficacy. The effect of rifampin on MPA metabolism can, at least in part, be explained by simultaneous induction of renal, hepatic, and gastrointestinal uridine diphosphate-glucuronosyltransferases and organic anion transporters with subsequent functional inhibition of enterohepatic recirculation of MPA.

Topics: Area Under Curve; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Enterohepatic Circulation; Glucuronosyltransferase; Heart-Lung Transplantation; Histiocytosis, Langerhans-Cell; Humans; Hypertension, Pulmonary; Male; Metabolic Clearance Rate; Middle Aged; Mycophenolic Acid; Pharmacology, Clinical; Respiratory Insufficiency; Rifampin; Tacrolimus; Time Factors; Uridine Diphosphate; Withholding Treatment

We report the first documented case of pulmonary toxicity to mycophenolate mofetil in this article.. A 51-year-old woman experienced systemic reactions beginning 10 days after cadaveric renal transplantation.. Recurrent respiratory failure and documented progressive pulmonary fibrosis ensued. Cultures were negative and other agents were discontinued. It was not until the mycophenolate was stopped did the patient improve.. Mycophenolate mofetil can cause acute respiratory failure simulating opportunistic infection or pulmonary edema. If not recognized, this may lead to the rapid development of severe pulmonary fibrosis, some of which may not be reversible.

Topics: Biopsy; Bronchoscopy; Female; Humans; Immunosuppressive Agents; Lung; Middle Aged; Mycophenolic Acid; Pulmonary Fibrosis; Respiratory Insufficiency